AUTHOR=Soerensen Sofie Forsberg , Wirenfeldt Martin , Wlodarczyk Agnieszka , Moerch Marlene Thorsen , Khorooshi Reza , Arengoth Dina S. , Lillevang Soeren Thue , Owens Trevor , Asgari Nasrin 

TITLE=An Experimental Model of Neuromyelitis Optica Spectrum Disorder–Optic Neuritis: Insights Into Disease Mechanisms

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.703249

DOI=10.3389/fneur.2021.703249

ISSN=1664-2295

ABSTRACT=Background: Optic neuritis (ON) is a common inflammatory optic neuropathy, which often occurs in neuromyelitis optica spectrum disease (NMOSD). An experimental model of NMOSD-ON may provide insight into disease mechanisms. 
Objective: To examine the pathogenicity of autoantibodies targeting the astrocyte water channel aquaporin-4 (AQP4-IgG) in the optic nerve. 
Materials and methods: Purified IgG from a AQP4-IgG positive NMOSD-ON patient was together with human complement (C) given to wild-type (WT) and type I interferon (IFN) receptor deficient mice (IFNAR1-KO) as two consecutive intrathecal injections into cerebrospinal fluid via cisterna magna. The optic nerves were isolated, embedded in paraffin and cut for histological examination and scored semiquantitatively in a blinded fashion. In addition, optic nerves were processed to determine selected gene expression by quantitative real-time PCR. 
Results: Intrathecal injection of AQP4-IgG+C induced astrocyte pathology in the optic nerve with loss of staining for AQP4 and glial fibrillary acidic protein (GFAP), deposition of C and demyelination as well as upregulation of gene expression for interferon regulatory factor-7 (IRF7) and CXCL10. Such pathology was not seen in IFNAR1-KO mice nor in control mice.
Conclusion: We describe induction of ON in an animal model for NMOSD and show a requirement for type I IFN signaling in the disease process.